Respiratory syncytial virus (RSV) is a common cause of infantile bronchiolitis, hospitalization, and long-term pulmonary morbidity. RSV-induced lung pathology is characterized by dramatic neutrophil influx, which contributes to epithelial injury, airway plugging and structural lung damage. Current management is entirely supportive, and no therapies are available that target RSV infection or inflammation. Our laboratory is interested in understanding the effects of protease-antiprotease imbalance on airway inflammation and remodeling seen in RSV disease. Specifically, the laboratory is focused on identifying a mechanistic role for protease dysregulation in RSV infection, and protease potentiation as a critical mechanism in RSV infection. We have recently shown that RSV infection of airway epithelia results in enhanced Matrix Metalloproteinase-9 (MMP-9) expression and release. We found high levels of dysregulated MMP-9 activity in lung secretions from children with RSV-induced respiratory failure. MMP-9 contributes to the generation of a novel neutrophil chemotactic peptide, proline-glycine-proline (PGP), which is derived from collagen breakdown. PGP binds to CXCR1 and CXCR2 on neutrophils, serving as a neutrophil chemoattactant in areas of dysregulated protease activity. The overarching objective of our current research is to determine the mechanisms by which RSV infection activates the MMP-9/PGP signaling cascade, resulting in persistent inflammation, leading to lung injury and clinical morbidity.
For more information contact:
Michele Kong, M.D.
Assistant Professor of Pediatrics
Pediatric Critical Care Medicine
The University of Alabama at Birmingham
Jarman F. Lowder Building, Suite 504
1600 7th Ave South, Birmingham, AL 35233